Conservative oxygen supplementation during helmet continuous positive airway pressure therapy in patients with COVID-19 and respiratory failure: a pilot study.

Background: Respiratory failure is a severe complication in coronavirus disease 2019 (COVID-19) pneumonia that, in addition to oxygen therapy, may require continuous positive airway pressure (CPAP) support. It has been postulated that COVID-19 lung injury may share some features with those observed in hyperoxic acute lung injury. Thus, a correct target arterial oxygen tension (P aO2 ) during oxygen supplementation may be crucial to protect the lung from further tissue damage. The aims of this study were: 1) to evaluate the effects of conservative oxygen supplementation during helmet CPAP therapy on mortality and intensive care unit (ICU) admission in patients with COVID-19 and respiratory failure, and 2) to evaluate the effect of conservative oxygen supplementation on new-onset organ failure and secondary pulmonary infections. Methods: This was a single-centre, historically controlled study of patients with severe respiratory failure due to COVID-19 pneumonia, receiving either conservative or nonconservative oxygen supplementation during helmet CPAP. A cohort receiving conservative oxygen supplementation was studied prospectively in which oxygen supplementation was administered with a target P aO2 <100 mmHg. Results of this cohort were compared with those of a cohort who had received liberal oxygen supplementation. Results: 71 patients were included in the conservative cohort and 75 in the nonconservative cohort. Mortality rate was lower in the conservative cohort (22.5% versus 62.7%; p<0.001). Rates of ICU admission and new-onset organ failure were lower in the conservative cohort (14.1% versus 37.3%; p=0.001 and 9.9% versus 45.3%; p<0.001, respectively). Conclusions: In patients with COVID-19 and severe respiratory failure, conservative oxygen supplementation during helmet CPAP was associated with improved survival, lower ICU admission rate and less new-onset organ failure.

The Role of Pulmonary Function Testing and Lung Imaging in the Long-Term Follow-Up of Patients with COVID-19 Pneumonia.

BACKGROUND: Post-COVID-19 Interstitial Lung Disease (PC-ILD) is characterized by fibrotic-like signs at high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) abnormalities after SARS-CoV-2 infection. It is still not clear how frequent these tests should be performed to rule out long-term consequences of COVID-19 pneumonia. OBJECTIVES: The aims of our study were to evaluate the incidence and risk factors of PC-ILD and possibly to propose a long-term follow-up program. METHOD: One-hundred patients, hospitalized in our ward for moderate to critical COVID-19, underwent two follow-up visits at three and 15 months in which PFTs and HRCT were performed. RESULTS: At the 15-month follow-up, 8% of patients showed residual radiological and functional signs consistent with PC-ILD. All but one of these patients had already demonstrated PFTs and HRCT alterations at first follow-up visit, and the last 1 patient showed worsening of lung function during follow-up. These findings highlight the negative predictive value of PFTs at 3-month follow-up for the development of PC-ILD. Aging, severity of COVID-19, and degree of pulmonary involvement during acute infection proved to be significant risk factors for developing PC-ILD. CONCLUSIONS: Our study highlights the importance of PFTs in the long-term follow-up of patients affected by moderate to critical COVID-19 pneumonia. Further studies are needed to confirm our hypothesis that HRCT should be performed only in patients with PFTs abnormalities.

Elexacaftor/tezacaftor/ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF), which is caused by mutations in the CF transmembrane conductance regulator (CFTR), is characterised by chronic bacterial lung infection and inflammation. In CF, monocytes and monocyte-derived macrophages have been shown to display defective phagocytosis and antimicrobial activity against relevant lung pathogens, including Pseudomonas aeruginosa. Thus, we addressed the effect of CFTR triple modulator therapy (elexacaftor/tezacaftor/ivacaftor (ETI)) on the activity of CF monocytes against P. aeruginosa. METHODS: Monocytes from people with CF (PWCF) before and after 1 and 6 months of ETI therapy were isolated from blood and infected with P. aeruginosa to assess phagocytic activity and intracellular bacterial killing. The oxidative burst and interleukin-6 secretion were also determined. Monocytes from healthy controls were also included. RESULTS: Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and lung microbiology by ETI. Both the phagocytic and microbicidal deficiencies of CF monocytes also improved significantly, although not completely. Furthermore, we measured an exuberant oxidative burst in CF monocytes before therapy, which was reduced considerably by ETI. This led to an improvement of reactive oxygen species-dependent bactericidal activity. Inflammatory response to bacterial stimuli was also lowered compared with pre-therapy. CONCLUSIONS: PWCF on ETI therapy, in a real-life setting, in addition to clinical recovery, showed significant improvement in monocyte activity against P. aeruginosa, which may have contributed to the overall effect of ETI on pulmonary disease. This also suggests that CF monocyte dysfunctions may be specifically targeted to ameliorate lung function in CF.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V'O2max), and O2 uptake at lactic acid threshold (V'O2@LT). RESULTS: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V'O2max, V'O2max/Kg and V'O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V'O2@LT, V'O2 @LT%, V'O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

Reliability of white blood cell scan in the follow-up of osteomyelitis.

INTRODUCTION: The question of whether antibiotic treatment does or does not affect reliability of white blood cell scan (WBCS) to detect disease activity in clinical practice is still unanswered. Our aim was to study the relationship between scintigraphic findings of WBCS and antibiotic therapy in a group of patients affected with osteomyelitis (OM). METHODS: We retrospectively reviewed 57 scans, performed in 18 patients affected by OM and who were on antibiotic treatment. The number of therapy weeks was calculated for each antibiotic. A comparison of results obtained during and after discontinuation of the antibiotic treatment was made. Overall sensitivity, specificity and accuracy of WBCS were calculated and compared with those obtained in patients undergoing therapy. RESULTS: Forty-seven scans were performed during treatment and 10 scans after discontinuation of treatment. The scintigraphic results obtained during and after discontinuation of treatment were as follows: TN 14 and 8, TP 31 and 2, FN 2 and 0, FP 0 and 0, respectively. Sensitivity, specificity and accuracy of WBCS, calculated in all patients, were 94.3%, 100% and 96.5% respectively. In patients receiving antibiotic therapy, the same parameters were 93.9%, 100% and 95.7% respectively. In patients treated with antibiotics that can decrease leukocyte function, there were 10 TN, 14 TP, 2 FN and 0 FP, while in patients treated with antibiotics that have not effect on leukocyte function there were 4 TN, 17 TP, 0 FN and 0 FP. CONCLUSION: The reliability of WBCS in the detection of disease activity during antibiotic treatment does not change significantly. It can be assumed that the influence of antibiotic therapy on labelled leukocyte behaviour is negligible.

In vitro activity of fosfomycin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy.

Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides.